SCLC, of which lymph nodes metastasis usually occurs in early stage, is a special kind of lung cancers. Although radiotherapy and chemotherapy have produced modest benefits in some patients, it would relapse and resistant to many drugs after traditional therapies. This is particularly important for early detection and providing reliable therapeutic target.
In this study, we verified SATB1 was overexpressed in the SCLC tissues and metastatic lymph nodes tissues, small interfering RNA targeting SATB1- SATB1- siRNA-1 and SATB1-siRNA-2 were constructed successfully, our results showed that transfection with SATB1- siRNA-1 or SATB1-siRNA-2 into the SCLC cell-NCI-H446, could inhibit the cells proliferation and invasion significantly. In addition, SATB1-SiRNA could induce the apoptosis of SCLC cells in vitro.
SATB1 was originally characterized as a regulator in T cell differentiation, found to be overexpressed in metastatic breast cancer cell lines and in human tissue specimens from advanced stages of breast carcinomas with metastasis
[2, 4, 19–21]. There are a few studies reported the expression of SATB1 in lung cancers, but the role of SATB1 is controversial: a study in squamous cell lung cancer and non-small cell lung cancers (NSCLC) showed that SATB1 expression was lost and the loss of SATB1 predicted poor prognosis in squamous cell carcinomas
, Zhou et al. showed the expression of SATB1 mRNA was much higher in NSCLC tissues with or without metastasis than in normal lung tissues
. In our study, we found SATB1 was highly expressed in SCLC tissues and metastatic lymphoid nodes tissues compared with lung cancer adjacent tissue, SATB1-siRNA could effectively inhibit SATB1 expression in SCLC cells. Treatment of SCLC cell lines with SATB1-siRNA resulted in morphologic changes in these cells. Our result also showed SATB1-siRNA could induce SCLC cells apoptosis after transfecting SATB1-SiRNA into SCLC cells. These results suggest SATB1 might be an ideal target for the treatment of SCLC. Metastasis is the final step in solid tumor progression and is the most common cause of death in cancer patients. Controlling the invasion and migration can improve the survival rate of cancer patients. Recent study demonstrated that the SATB1 plays an important role in the process of invasion and migration. Consistent with the previous study, our results also showed the invasion ability of SCLC cells declined obviously after transfected with SATB1-SiRNA.
About the mechanisms why SATB1 influence the proliferation and invasion for small lung cancer cell, so far there is no much research on that, however, lots of study about the roles of SATB1 in breast cancer and other cancers have been investigated, Han et al. use gene chip to find SATB1 can induce the change of more than 1000 genes’ expression
. Some are associated with cancer invasion and metastasis, such as MMP2, MMP9, CTGF, et al.
. We will further study its detailed mechanism in the small lung cancer cell.
In summary, our work provides a better understanding of the physiological role of SATB1 in SCLC, SATB1 could regulate the invasion and migration of SCLC cells, this may provide important clues for more effective targeting of SCLC and other cancers with aberrant SATB1 activation.